This invention relates to the sterilization of liquid barrier transfer couplings for use in the pharmaceutical manufacturing industry.
Many pharmaceutical manufacturing facilities develop from small scale operation. Nevertheless the manufacturing standards, controls and protocols imposed by, for example, the Medical Control Agency in the United Kingdom and the Federal Drug Administration in the United States, are of necessity the same whatever the size of facility. These are established around such general needs as that for the aseptic particulate and microbiological conditions to be maintained in the zone immediately surrounding a product whenever the product will otherwise be exposed to the environment. There is a need for absolute barrier technology and automatic systems to be used to minimize human interventions in processing areas thereby to produce significant advantages in assurance of sterility of manufactured products.
The economics of manufacture have influenced how closed solution manufacturing vessels may be installed in a relatively low grade environmental area. Manufactured solutions are pumped through barriers such as sterile area walls or containment isolators to vial filling machines. The interconnecting pipework between vessel and filling machine and also recirculation pipework are normally permanently installed continuous stainless steel pipes to enable steam sterilisation to be carried out. The pipework is designed to self-drain and is rated to withstand the operating pressure and to meet statutory requirements for pressure testing.
Efficient utilisation of the plant has resulted in a demand for a number of processing vessels to feed more than one filling machine. The consequent provisions for switching over of pipe connections are complex to engineer, requiring pipe manifolds and considerable numbers of valves. Silicone piping linked as required from a nominated process vessel to a designated vial filling machine offers an attractive measure of cost reduction, flexibility of operation and general weight reduction. It is readily cleaned and may be sterilised. However, the piping must subsequently be connected aseptically both to a filling machine and to a process vessel. The connection techniques currently available are frequently not acceptable in not meeting standards imposed by control agencies or even for general reasons of quality assurance.
A particular way in which such flexible silicone piping might be employed would be for it to be used for transferring a manufacturing batch to a filling apparatus after which it would be subjected to in situ washing and sterilization. Steam sterilization in an autoclave would be the recommended approach but such piping is not pressure rated and, as such, cannot be steam sterilized using conventional pressurised steam sterilizing technology.